A novel approach to high-throughput quality control of parallel synthesis libraries |
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Authors: | Shah N Gao M Tsutsui K Lu A Davis J Scheuerman R Fitch W L Wilgus R L |
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Affiliation: | Affymax Research Institute, Santa Clara, California 95051, USA. |
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Abstract: | Combinatorial chemistry is a powerful tool to enhance drug discovery efforts in the pharmaceutical industry. One type of combinatorial chemistry, parallel synthesis, is now widely used to prepare numerous compounds of structural diversity. A novel high-throughput method for quality control of parallel synthesis libraries has been developed. The method uses flow injection MS, for proof of structure and estimation of purity, and a novel direct injection CLND technique for quantitation of amount. Following the synthesis of a small molecule library, compounds analyzed using this technique were characterized by mass spectrometry, and an accurate concentration of the compound was assessed by CLND. Characterization of one compound is completed in 60 s, allowing for up to 1000 compounds to be analyzed in a single day. The data is summarized using pass/fail criteria using internally developed software. |
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